Effector cells mediating broadly reactive anti-tumor cytotoxic activty, induced under syngeneic conditions in vitro in normal mouse spleen cells by polyinosinic acid, are closely related to natural killer cells as judged by expression of cell surface differentiation antigens and target cell specificity. The response is controlled by multiple genes. Similar activity is generated by thymocytes stimulated in vitro by both polyinosinic acid and supernatants of Con A-stimulated cells. The expression of MHC determinants on normal mouse spleen cells has been modulated by in vitro enrichment or depletion of membrane sterol content, as documented by fluorescent antibody probes and quantitative flow microfluorometry.